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Hyperprolactinemia (1 of 9)

Hyperprolactinemia (1 of 9)

Hyperprolactinemia (1 of 9)

1 Patient presents w/ signs & symptoms suggestive of hyperprolactinemia

2 DIAGNOSIS • Rule out physiologic causes • Identify common conditions that give rise to hyperprolactinemia

Is tumor SUSPECTED suspected or Tumor is no obvious cause suspected identifi ed? See next page

Cause identifi ed

HYPOTHYROIDISM DRUGINDUCED RENAL FAILURE HYPOTHALAMIC PITUITARY STALK DAMAGE

A Cause-specifi c A Cause-specifi c A Cause-specifi c A Cause-specifi c treatment treatment treatment treatment • Levothyroxine • If possible, • Treat underlying • Treat underlying (T4) replacement discontinue cause cause off ending medication • agonist may be added to restore normoprolactinemia & alleviate © symptomsMIMS

Not all products are available or approved for above use in all countries. Specifi c prescribing information may be found in the latest MIMS.

B136 © MIMS 2020 HYPERPROLACTINEMIA 1 C B Various the estrogen forspecifi latest replacement MIMS see are available. Please products c formulations. Pharmacological therapy Pharmacological therapy Non-pharmacological • • SYMPTOMS & DESIRE &DESIRE SYMPTOMS women Estrogen replacement in Watchful observation ASSESS PRESENT PRESENT ASSESS symptoms (fertility (fertility symptoms FOR FERTILITY FOR Microadenoma is notdesired) is Minimal Minimal ©1 MIMS Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing SUSPECTED PROLACTINOMA SUSPECTED Hyperprolactinemia (2of9) FURTHER EVALUATIONFURTHER have microadenoma have microadenoma (fertility is desired) is (fertility macroadenoma macroadenoma Asymptomatic Asymptomatic prolactinoma prolactinoma Does patient Does TREATMENT (≤10 mm)or confi rmed? (>10 mm)? See page 3 page See B137 SIZE Yes 3 Is No HYPERPROLACTINEMIA Macroadenoma TREATMENT See page 4 page See IDIOPATHIC © MIMS 2020 HYPERPROLACTINEMIA TREATMENT © CONTINUE MIMS Yes Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing Hyperprolactinemia (3of9) C (PRL) levels within within (PRL) levels Prolactin MICROPROLACTINOMA MICROPROLACTINOMA PRL levels within normal normal within PRL levels FERTILITY DESIRED FERTILITY Pharmacological therapy Pharmacological C E TREATMENT FOR • ASYMPTOMATIC ASYMPTOMATIC range (<30ng/mL)? range normal range (<30 range normal Dopamine agonist Dopamine Considersurgery FOLLOWUP FOLLOWUP • therapy Pharmacological agonists dopamine Try different ng/mL)? B138 D D No No TREATMENT Yes CONTINUE © MIMS 2020 HYPERPROLACTINEMIA C CONTINUE TREATMENTCONTINUE • therapy Pharmacological Try different dopamine agonists Tumor & shrinkage normalization of normalization FOLLOWUP PRL levels? Yes © MIMSD Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not No Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing C B D Hyperprolactinemia (4of9) MACROPROLACTINOMA Pharmacological therapy Pharmacological therapy Non-Pharmacological Follow-up • • No • • Dopamine Formal fi visual eld testing normalization ofPRL normalization PRL levels PRL 4months within MRI Repeat Tumor & shrinkage TREATMENT OF RESULTS levels? B139 E Consider surgery CONTINUE TREATMENTCONTINUE Yes © MIMS 2020 HYPERPROLACTINEMIA • • • Disorders Neurogenic • • • • • • • • • • • • • Men • • • • • • • Women • &Symptoms Signs • • • • • Drug-induced • • • • • • • Physiologic Etiology Stimulation ofbreast Spinal cord injury onthe wall chest Lesions Anticonvulsants Phenytoin eg Anesthetics - inhibitor(SSRI) reuptake Selective Verapamil - antagonists Ca Estrogens eg Hormones , eg Imipramines Reserpine - depletors Catecholamine Ranitidine Osteopenia, decreased muscle mass & decreased facial hairmay facial hyperprolactinemia occur inprolonged &decreased muscle mass decreased Osteopenia, Oligospermia - Impotence - Reduced - suppression Gonadotropin True isuncommon galactorrhea Hypogonadism muscle weakness Extraocular - compression Visual opticnerve by caused loss libido Diminished pronounced mineral hyperprolactinemia invertebral density insustained, bone Reduction oflibido Loss Dyspareunia Vaginal dryness Infertility Galactorrhea irregularity Menstrual tumor fi may visual cause apituitary For sexes, both orheadache eld defects levels prolactin (PRL) isthe presenceHyperprolactinemia ofelevated H &opiateOpiates antagonists Methyldopa - inhibitors synthesis Dopamine - eg Butyrophenones - - - blockers receptor Dopamine Exercise Coitus Sleep Stress stimulation wall Chest Lactation Pregnancy 2 eg , Phenothiazines Chlorpromazine, eg  ioxanthines © antagonists-receptor (H MIMS Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing 2 RA) eg Cimetidine, eg RA) 1 Hyperprolactinemia (5of9) HYPERPROLACTINEMIA 2 DIAGNOSIS B140 • • • • • • Prolactin ofEctopic Production • • • • • • • • • Damage Stalk Hypothalamic-Pituitary • • • • • Hypersecretion Pituitary • • • • • • Disorders Systemic Uterine cervical carcinoma Uterine cervical Gonadoblastoma teratomas Ovarian Renal cell carcinoma adenocarcinoma Colorectal lymphoma Non-Hodgkin Infi ltrations Granulomas surgery) Trauma suprasellar stalksection, (eg pituitary Irradiation Rathke’s cyst hypophysitis Lymphocytic Adenoma w/stalkcompression Empty sella meningioma) metastases, hypothalamic Tumors germinoma, (eg craniopharyngoma, Macroadenoma (compressive) adenoma Plurihormonal Macroprolactinemia >100mcg/L) levels commonProlactinoma (most ofprolactin cause Acromegaly Pseudocyesis disease ovarian Polycystic Epileptic seizures Cirrhosis Chronic renal (CRF) failure Hypothyroidism © MIMS 2020 HYPERPROLACTINEMIA • • • • • • • TestsLab Exam &Physical Diagnosis • • Evaluation Radiologic • • (PRL) Level Fasting Prolactin Measure • • Hypothyroidism • Damage Hypothalamic Irreversible • Lesions Mass orSellar Hypothalamic • InfiGranulomatous ltrates Damage Stalk Hypothalamic-Pituitary • • FailureRenal • • stopmedication: whocannot patients Psychiatric • Hyperprolactinemia Drug-induced • - MRI & CT scan normal & no obvious cause, patient cause, &noobvious issaidtohave normal idiopathic scan hyperprolactinemia & CT MRI - -  outhypothyroidism) (torule tests function yroid To polyethylene glycol outmacroprolactinemia, rule precipitation isrecommended test Pregnancy factor-1) necessary insulingrowth as cortisol, (eg levels, testosterone hormones Other pituitary creatinine] nitrogen urea (BUN), [blood chemistry Blood history Drug - fi visual forgalactorrhea, Check pattern onthe hairgrowth body, etc ofcirrhosis, signs eld defects, - examination including &physical exam cranialnerve history Careful confi the limits upper above Alevel therms diagnosis - To tohave itisrecommended PRL asinglemeasurement ofserum ofhyperprolactinemia, establish the diagnosis - Serum PRL >200 ng/mL indicates prolactinoma >200ng/mLindicates PRL Serum - w/contrast used may be tomography Computed also (CT) - enhancement w/gadolinium (MRI) resonance imaging Magnetic isthe study imaging ofchoice - &iftumor ofhyperprolactinemia issuspected ifthere cause isnoobvious performed Should be madetoconfi shouldbe measurements Several diagnosis rm - <100ng/mL likely level Aprolactinoma isless w/PRL - prolactinoma out) usually indicates ruled >250 ng/mL (w/ physiologic causes & drug-induced range: Diagnostic level PRL fasting <30ng/mLnormal range: Normal extensive outbefore evaluation ruled be should hyperprolactinemia hypothyroidism &drug-induced tumors, renal parasellar failure, Physiologic causes, Levothyroxine (T Levothyroxine No treatment necessary may be hyperprolactinemia may reverse Surgical resection Glucocorticoids (rarely effective) Renal transplant may tonormal help levels torestore PRL Treat underlying cause itmay condition Use underlying psychiatric w/caution worsen as - symptoms torestore normoprolactinemia agonist &alleviate added mayDopamine be ofoff dose decrease slowly If possible, orsubstitute analternativeending drug medications  PRL measurement ofserum en, repeat - discontinueIf possible, off for3daysending orsubstitute analternative medication drug information management chart forfurther disease Hypothyroidism see Please adequate thyroid usuallyoccurs after ofhyperprolactinemia replacement Resolution - compression tostalk secondary hyperprolactinemia usuallyindicates mass <200ng/mLw/large PRL pituitary Serum Physician must decide whether a radiographic study is warranted if PRL level <250 ng/mL but>100 Physician level if PRL mustwhether studya radiographic decide is warranted - are classifi Prolactinomas - macroadenoma ifthe is≥10mm;microadenoma as size if<10mminsize ed A CAUSE-SPECIFIC TREATMENT (HYPERPROLACTINEMIA) 4 © MIMS) Replacement Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing 3 2 Hyperprolactinemia (6of9) FURTHER EVALUATION FURTHER DIAGNOSIS (CONT’D) B141 © MIMS 2020 HYPERPROLACTINEMIA • • • • • • • • Agonists Dopamine • • • • Formal Visual Field Testing • • • Watchful Observation - Surgical decompression may be used if vision isthreatened ifvision Surgical decompression used may be - occurs &explaintopatient iftumor &benefi growth the Bromocriptine risks Restart oftreatmentts - Visual field inpatients is recommended testing w/macroadenomas - fi visual Regular isrecommended eld throughout exam pregnancy - isnotuseful levels ofPRL &monitoring progressively inpregnancy rise levels PRL - pregnancy may during &15-30%ofmacroadenomas 5%ofmicroadenomas grow - 2optionsare recommended: Inwomen w/larger macroadenomas, - - - Attempt tothe drug toreduce exposure neonatal - women inhyperprolactinemic torestore fertility used been has Bromocriptine Pregnancy: isnottolerated intravaginally administered iforaldose May be ~5%ofpatients donothave recurrence w/discontinuation ofBromocriptine - Discontinuation disturbances alongw/the ofvisual risk inrecurrent &tumor hyperprolactinemia regrowth results women in80-90%ofhyperprolactinemic &ovulation Resumption ofmenses - disturbances &visual Headaches improve rapidly days within ofcommencing therapy - in40%ofpatients shrinkage of ≥50%isobserved Macroadenomas - gonadal tumor &restores function size Decreases - Eff ects: ErgotActions: alkaloidthat bindsto&stimulates D ofchoiceInitial drug ormacroadenomas microadenomas  inpatients tumor&restore gonadal size w/ function decrease levels, erapy PRL tolower recommended Titrate function &torestore suppression reproductive PRL maximum toachieve dose discontinueIf possible, offending medication symptoms &toalleviate levels PRL istodecrease Goal fi w/visual More initiallyinthose frequent monitoring eld defi cit 6-12months todopamineagonist thereafter prior treatmentPerformed &every studies at Imaging intervals yearly - ifasignifi performed shouldbe MRI isnoticed inPRL cant rise - doneregularly shouldbe levels PRL Serial - ifitisgrowing todetermine ofthe adenoma isnecessary observation Close Eff ects: symptoms Appropriate are notconcerned inpatients w/fertility, whopresent w/microadenomas, &have minimal - Give Bromocriptine continuously risk Bromocriptine fetal Give w/theoretical throughout gestation, however - Discontinue Bromocriptine - signifi extension orparasellar cant suprasellar Bromocriptine can be safely discontinued in women w/ microadenomas or intrasellarwithout macroadenomas forconception (toallow have occurred timing) cycles menstrual Woman contraception barrier until pregnant shoulduse 3regular tobecome &Bromocriptine desiring Lowers serum PRL levels in70-100%ofpatients levels PRL serum Lowers period Studies that a4-6year over have donotgrow shown 93%ofmicroadenomas B NON-PHARMACOLOGICAL THERAPY (PROLACTINOMA) C

© MIMS PHARMACOLOGICAL THERAPY (PROLACTINOMA) Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing Hyperprolactinemia (7of9) B142 2 dopamine-receptors onlactotroph dopamine-receptors cells © MIMS 2020 HYPERPROLACTINEMIA • • • • • • • • • • • • • Radiotherapy • • • • • Indications: • Transsphenoidal Surgery • • • Indicated for use in hyperprolactinemic amenorrhea inhyperprolactinemic foruse Indicated ErgotActions: which adopamineagonist derivative isboth &aserotonin antagonist disease heart ofvalvular Discontinued risk inother countries duetoincreased Tolerance issimilartoBromocriptine - Eff ects: Effi- agonists is similartootherDopamine cacy Eff ects: Non- agonistActions: Dopamine inpatients whoare useful intolerantMay be ofergot derivatives tumor in~70%ofmacroadenomas &shrinks PRL Normalizes - in~80%ofpatients gonadal &restores w/microadenomas function levels PRL serum Lowers - Eff ects: cells Actions: Actions: Higher effi tumor shrinkage ofpituitary - &higher frequency levels PRL innormalizing cacy Fewer sideeff twice aweek given be &can than Bromocriptine ects - inpatientsUseful whoare resistant orintolerant toBromocriptine It eff may forthe require 20years maximal tonormal levels restore PRL &may never achieved tobe ect May control tumor growth prolactinomas inpatients treatmentRecommended surgical whofail orwhohave aggressive,resistant or malignant Morbidity rate: 0.4% - rate: Mortality 0.3% - surgeons experienced by UsuallyPotential infrequent when complications: performed ofmacroprolactinomas follow-up Recurrence rates reach 50%inlong-term - - Only30%are successfully resected Macroprolactinomas: - normalization PRL Initially 70%achieve Microprolactinomas: - Eff ects: Patients w/tumors onthe pressing opticchiasm treatmentPatients medical isnotacceptable w/intrasellar tumor &long-term Patients therapy whoare resistant toorexhibitnon-tolerance tooptimalmedical Craniotomy israrely performed - method Preferred Evaluate ofgalactorrhea menstruation &resolution likeresumption symptoms ofcyclic tumor w/MRI Check size levels PRL serum Monitor fasting Recurrence of microprolactinomas & macroprolactinomas occurs in 20% of patients within 1 year ofsurgery 1year Recurrence ofmicroprolactinomas¯oprolactinomasoccursin20%patients within Several studies have shown that studieshave shown Pergolide Several effi isas Bromocriptine as cacious toQuinagolide ~50%ofpatients respond whoare resistant toBromocriptine Suppresses PRL secretion for >14 days after asingleoraldose for>14days after secretion PRL Suppresses Ergot which isalong-actingdopamineagonist derivative w/highaffinity forD C © MIMS PHARMACOLOGICAL THERAPY (PROLACTINOMA) (CONT’D) Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing Hyperprolactinemia (8of9) OTHER TREATMENT D E FOLLOW-UP SURGERY B143 2 receptors on lactotroph onlactotroph receptors © MIMS 2020 HYPERPROLACTINEMIA Quinagolide Pergolide Metergoline Cabergoline Bromocriptine Drug Products listed above may not be mentioned in the disease management chart but have been have but chart management disease the in mentioned be not may above listed Products placed here based on indications listed in regional manufacturers’ product information. product manufacturers’ regional in listed indications on based here placed & non-elderly adults w/ normal renal & hepatic function unless otherwise stated. otherwise unless function &hepatic renal w/ normal adults & non-elderly 900 mcg/day PO 900 mcg/day PO dose: Max ofnot<4wkupto intervals titrate inincrements of75-150 mcgat (>300 mg/day), are needed If higher doses 24hrly 75-150 mcgPO dose: Maintenance 3-day intervals inincrements dose of25mcgat Increase 24hrly x3days 25 mcgPO dose: Initial 24hrly 50-150 mcgPO dose: Maintenance &fornot<90days recur menses 8hrly until 4mgPO dose: Maintenance to then increase 8hrly x3-4days 2mgPO dose: Initial 0.25-2mg/wk dose: Maintenance 0.5 mg/wkat mthly intervals inincrements slowly of dose May increase in1-2doses 0.5 mg/wkPO dose: Initial 30mg/day dose: Max 5-7.5mg/day PO dose: Maintenance 12hrly wk to10-20mgPO ofseveral aperiod over increase Gradually 8-12hrly 1.25 mgPO 12hrly or 2.5mgPO dose: Initial All dosage recommendations are for non-pregnant & non-breastfeeding women, women, &non-breastfeeding non-pregnant for are recommendations dosage All © MIMS Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing Please see the end of this section for the reference list. reference the for section this of end the see Please Dosage Hyperprolactinemia (9of9) Dosage Guidelines DOPAMINE AGONISTS B144 • • Instructions Special • • Reactions Adverse disorders ofhypertensive women w/history disorders &inpostpartum psychiatric disease, Use w/caution inpatients w/CV Take nausea tominimize w/food Bromocriptine tolerated than better may Quinagolide be Studies that have shown Cabergoline & mouth) congestion, dry nasal fi thickening pleural &effbrosis, usions, Otherconfusion); eff (retroperitoneal ects delusions, hallucinations, psychosis, eff effusions); CNS (headache, ects pericardial pericarditis, erythromelalgia, arrhythmias, hypotension, eff prolonged (vasospasm, ects CV &orthostatic hypotension); syncope sideeffDose-related (N/V, ects dizziness, Remarks © MIMS 2020

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